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Clinical characterization of colitis arising from anti-PD-1 based therapy

2018; Landes Bioscience; Volume: 8; Issue: 1 Linguagem: Inglês

10.1080/2162402x.2018.1524695

2162-402X

Daniel Wang, Meghan J. Mooradian, Dae Won Kim, Neil J. Shah, Sarah E. Fenton, Robert M. Conry, Rutika Mehta, Ann W. Silk, Alice Y. Zhou, Margaret Compton, Rami N. Al‐Rohil, Sunyoung Lee, Amber L. Voorhees, Lisa Ha, Svetlana B. McKee, Jacqueline Norrell, Janice M. Mehnert, Igor Puzanov, Jeffrey A. Sosman, Sunandana Chandra, Geoffrey T. Gibney, Suthee Rapisuwon, Zeynep Eroglu, Ryan J. Sullivan, Douglas B. Johnson,

Drug-Induced Adverse Reactions

Colitis is a frequent, clinically-significant immune-related adverse event caused by anti-programmed death-1 (PD-1). The clinical features, timing, and management of colitis with anti-PD-1-based regimens are not well-characterized. Patients with advanced melanoma that received either anti-PD-1 monotherapy ("monotherapy") or combined with ipilimumab ("combination therapy") were screened from 8 academic medical centers, to identify those with clinically-relevant colitis (colitis requiring systemic steroids). Of 1261 patients who received anti-PD-1-based therapy, 109 experienced colitis. The incidence was 3.2% (30/937) and 24.4% (79/324) in the monotherapy and combination therapy cohorts, respectively. Patients with colitis from combination therapy had significantly earlier symptom onset (7.2 weeks vs 25.4 weeks, p < 0.0001), received higher steroid doses (median prednisone equivalent 1.5 mg/kg vs 1.0 mg/kg, p = 0.0015) and experienced longer steroid tapers (median 6.0 vs 4.0 weeks, p = 0.0065) compared to monotherapy. Infliximab use and steroid-dose escalation occurred more frequently in the combination therapy cohort compared to monotherapy. Nearly all patients had resolution of their symptoms although one patient died from complications. Anti-PD-1 associated colitis has a variable clinical presentation, and is more frequent and severe when associated with combination therapy. This variability in checkpoint-inhibitor associated colitis suggests that further optimization of treatment algorithms is needed.